Peony-Glycyrrhiza Decoction (PGD) for Antipsychotic-induced Hyperprolactinemia in Patients With Schizophrenia

NCT01852331 | Completed Phase 2 DMC

• 1 other identifier: UW 11-274
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 4

Brief Summary

The investigators hypothesize that Peony-Glycyrrhiza Decoction (PGD) adjunctive therapy could reduce the incidence of prolactin (PRL)-related adverse events in patients with schizophrenia and suppress antipsychotic-induced elevation of PRL levels. This is a placebo-controlled trial conducted in schizophrenic patients to determine whether PGD adjunctive treatment could produce greater biochemical and clinical improvement on hyperprolactinemia (hyperPRL) compared to placebo treatment.

Conditions

Schizophrenia; Schizophrenic Disorder; Hyperprolactinemia; Hyperprolactinaemia

Keywords

Schizophrenia; Schizophrenic Disorder; Hyperprolactinemia; Hyperprolactinaemia; Chinese herbal medicine; Traditional Chinese medicine; Peony-Glycyrrhiza Decoction; PGD; Glycyrrhiza Radix; Liquorice Root; Gancao; Paeoniae Alba Radix; White Peony Root; Baishao

Outcome Measures

Primary Outcomes (4)

• Changes from baseline Positive and Negative Syndrome Scale (PANSS) at 8 weeks and 16 weeks

  The severity of psychotic symptoms will be assessed using the Positive and Negative Syndrome Scale (PANSS)

  baseline, week 8 and week 16

• Changes from baseline Clinical Global Impression (CGI) score at 8 weeks and 16 weeks

  The severity of psychotic symptoms will be assessed using the Clinical Global Impression (CGI).

  baseline, week 8 and week 16

• Changes from baseline Simpson-Angus Rating Scale (SAS) at 8 weeks and 16 weeks

  The Simpson-Angus Rating Scale (SAS) will be used to evaluate antipsychotic-induced abnormal involuntary movement symptoms.

  baseline, week 8 and week 16

• Changes from baseline Abnormal involuntary movement scale (AIMS) at 8 weeks and 16 weeks

  The abnormal involuntary movement scale (AIMS) will be used to evaluate antipsychotic-induced abnormal involuntary movement symptoms.

  baseline, week 8 and week 16

Secondary Outcomes (2)

• Change from baseline scores of Prolactin Related Adverse Event Questionnaire (PRAEQ) at 8 weeks and 16 weeks

  baseline, week 8 and week 16

• Change from baseline scores of Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at 8 weeks and 16 weeks

  baseline, week 8 and week 16

Other Outcomes (3)

• Changes from baseline serum prolactin levels at 8 weeks and 16 weeks

  baseline, week 8 and week 16

• Changes from baseline serum estradiol levels at 8 weeks and 16 weeks

  baseline, week 8 and week 16

• Changes from baseline serum testosterone levels at 8 weeks and 16 weeks

  baseline, week 8 and week 16

Study Arms (2)

PGD granules

ACTIVE COMPARATOR

While continuing current antipsychotic medications, subjects will receive adjunctive Peony-Glycyrrhiza Decoction (PGD) granules (equivalent to 45 g raw materials in total per day). They need to take the granules two times a day, each time one sachet (aluminum foil pack of 9g, tear open and empty contents into a cup, add 200ml hot water, stir until dissolute completely, and drink the preparation when warm), for a consecutive of 16 weeks.

Drug: PGD granules

Placebo

PLACEBO COMPARATOR

While continuing current antipsychotic medications, subjects will receive adjunctive treatment with placebo granules. They need to take the placebo granules two times a day, each time one sachet (aluminum foil pack of 9g, tear open and empty contents into a cup, add 200ml hot water, stir until dissolute completely, and drink the preparation when warm), for a consecutive of 16 weeks.

Drug: Placebo

Interventions

PGD granules DRUG

The preparation of Peony-Glycyrrhiza Decoction (PGD) granules is in compliance with Pharmacopoeia of the People's Republic of China and Good Manufacturing Practice (GMP). Briefly, sliced, broiled Paeoniae Alba Radix and Glycyrrhizae Radix in a ratio of 1:1 in weight will be immersed and boiled in an 8-fold volume of distilled water for 2.5 hours. This process will be repeated twice. The extract solution will be pooled and concentrated into granule form. Weight of the resulting granules contained in two 9g-sachet packs (to be taken in one day) is equivalent to 45 g raw herbal materials which are supplied for one day.

PGD granules

Placebo DRUG

The placebo granules are prepared to be identical to PGD granules in smell, taste and color.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• have a primary diagnosis of schizophrenia or schizoaffective disorder based on International Classification of Diseases (10th edition);
• under antipsychotic medications for at least three months and current conditions are stable, indicated by no difficulty to communicate with investigators and give informed consent;
• have developed at least one overt hyperPRL-associated symptom, including oligomenorrhoea (infrequent, irregularly timed episodes of bleeding occurring at intervals of more than 35 days from the previous menstrual cycle), amenorrhoea (the absence of menstruation for three menstrual cycles or 6 months), galactorrhea, decreased libido, anorgasmia or erectile dysfunction; and
• serum PRL levels are \>24 ng/ml (or 1043.472 pmol/l) in female or \>19 ng/ml (or 826.082 pmol/l) in male.

You may not qualify if:

• unstable medical conditions;
• suicidal ideas or attempts or aggressive behavior;
• history of alcoholism in the past one year, characterized by compulsive and uncontrolled consumption of alcohol, despite the realization of its negative effects on health, relationship, and social standing;
• history of drug abuse in past one year;
• currently treated with Chinese medicine or other natural products;
• allergic history of herbal medicine;
• pre-existing hyperPRL symptoms not associated with antipsychotic treatment; and
• pregnant and lactating women and those who refuse to use contraception during the study.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Kowloon Hospital, Hong Kong: collaborator
• Queen Mary Hospital, Hong Kong: collaborator
• Capital Medical University: collaborator
• Xijing Hospital: collaborator

Study Sites (4)

Xijing Hospital

Xian, Shanxi, 710032, China

Location

Beijing Anding Hospital

Beijing, 100088, China

Location

Department of Psychiatry, Queen Mary Hospital

Hong Kong, China

Location

Department of Psychiatry, Kowloon Hospital

Kowloon, China

Location

Related Publications (1)

• Man SC, Li XB, Wang HH, Yuan HN, Wang HN, Zhang RG, Tan QR, Wong HK, McAlonan GM, Wang CY, Zhang ZJ. Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial. J Clin Psychopharmacol. 2016 Dec;36(6):572-579. doi: 10.1097/JCP.0000000000000607.

  PMID: 27755159 DERIVED

MeSH Terms

Conditions

Schizophrenia; Hyperprolactinemia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Zhang-Jin Zhang, MMed, PhD

  School of Chinese Medicine, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 13, 2013
• Study Start: January 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 7, 2015

Record last verified: 2015-05

Locations

CN (4)